| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | August 1, 1995 |
| PATENT TITLE |
Liquid polymer composition, and method of use |
| PATENT ABSTRACT | The invention relates methods for the treatment of gingivitis, oral plaque and oral or dermatological fungal infections by the administration of a liquid methacrylic acid copolymer composition that contains a release adjusting agent and a pharmacological agent. The composition forms a solid film upon drying, and is capable of accomplishing the sustained release of the pharmacological agent such as to permit its use in the treatment or prevention of dental or dermatological conditions |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | January 4, 1993 |
| PATENT REFERENCES CITED |
Kristl, J. et al., "Physikalische Eigenschaften von Eudispert-Poly-elektrolytsystemen und ihre In-vitro-Wirkstoffliberation", Acta Pharm. Technol., 33(3):140-144 (1987). Translation of Kristl, J. et al., "Physikalische Eigenschaften von Eudispert-Poly-elektrolytsystemen und ihre In-vitro-Wirkstoffliberation", Acta Pharm. Technol., 33(3):140-144 (1987). Dittgen, M. et al., "Untersuchung von Polyacrylat- und Polymethacrylathydrogelen", Pharmazie, 41:883-884 (1986). Translation of Dittgen, M. et al., "Untersuchung von Polyacrylat- und Polymethacrylathydrogelen", Pharmazie, 41:883-884 (1986). Von W. Kern, B. et al., Hagers Handbuch Der Pharmazeutischen Praxis Fur Apotheker, Arzneimittelhersteller Artze Und Medizinalbeamte, Springer-Verlag, Berlin, 1977 [pp. 402-403]. Translation of Von W. Kern, B. et al., Hagers Handbuch Der Pharmazeutischen Praxis Fur Apotheker, Arzneimittelhersteller Artze Und Medizinalbeamte, Springer-Verlag, Berlin, 1977 [pp. 402-403]. Addy, M., et al., The effects of a 0.2% chlorhexidine gluconate mouthrinse on plaque, toothstaining and candida in aphthous ulcer patients, J. Clin. Periodontal., 14:267-273 (1987). Addy, M., et al., Use of chlorhexidine gluconate and povidone iodine mouthwashes in the treatment of acute ulcerative gingivitis, J. Clin. Periodontol., 5:272-277 (1978). Afflitto, J., et al., Effects of Tetrapotassium Peroxydiphosphate (KPDP) on Plaque/Gingivitis In Vivo, J. Dent. Res., 67 (Spec. Issue Mar.):401, abstract 2309 (1988). Bossche, H. V., et al., Anti-Candida Drugs--The Biochemical Basis For Their Activity, CRC Critical Reviews n Microbiology, 15(1):57-72 (1987). Cameron, J. A., The use of ultrasound and an EDTA-urea peroxide compound in the cleansing of root canals. An SEM study, Australian Dental Journal, 29(2):80-85 (1984). Ciancio, S. G., et al., The Effect of a Quaternary Ammonium-Containing Mouthwash on Formed Plaque, Pharmacology and Therapeutics in Dentistry, 3:1-6 (1978). Wood, D. A., Biodegradable Drug Delivery Systems, International Journal of Pharmacertics, 7:1-18 (1980). Chafi, N., et al., Preparation and Study of Oral Galenic Forms By Dispersing Into Eudragit/Matrix a Polyacryloyl-Acetylsalicylic Anhydride, Drug Development and Industrial Pharmacy, 15:629-648 (1989). Chang, R. K., et al., Preparation and Preliminary Evaluation of Eudragit RL and RS Pseudolatices For Controlled Drug Release, Drug Development and Industrial Pharmacy, 15(3):361-372 (1989). Chivian, N., Endodontics An Overview, Dental Clinics of North America, 28(4):637-649 (1984). Friedman, M., et al., New sustained release dosage form of chlorhexidine for dental use, Journal of Periodontal Research, 17:323-328 (1982). Friedman, M., et al., Sustained Release Chlorhexidine Preparations for Topical Use, IADR Abstracts, p. 905, Abstr. 72 (1980). Friedman, M., et al., Plaque Inhibition by Sustained Release of Chlorhexidine from Removable Appliances, Journal of Dental Research, 64(11):1319-1321 (1985). Goodson, J. M., in Medical Applications of Controlled Release, vol. II, Langer, R. S. et al., Eds., CRC Press Inc., (1984), 115-138. Goto, S., et al., Evaluation of the sustained release properties of Eudragit RS, RL and S (acrylic resins) microcapsules containing ketoprofen in beagle dogs, J. Microencapsulation, 5:343-360 (1988). Kostiala, I., et al., Oral mycoses and their treatment, Acta Odontol. Scand., 37:87-101 (1979). Thoennes, C. J., et al., Evaluation of a Rapidly Disintegrating Moisture Resistant Lacquer Film Coating, Drug Development and Industrial Pharmacy, 15(2):165-185 (1989). Soskolne, A., et al., New sustained release dosage form of chlorhexidine for dental use, Journal of Periodontal Research, 18:330-336 (1983). |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A method of removing or inhibiting the buildup of oral plaque, said method comprising topical application of an efficacious amount of a liquid polymer composition to the teeth or gingival tissues of an animal or human, said liquid polymer composition consisting essentially of: (a) one or more sustained release acrylic polymers; (b) a bacteriocidal pharmacological agent; (c) a release adjusting agent selected from the group consisting of a cross-linking agent, citric acid, a sodium citrate, sodium docusate, and an amino acid; and (d) a pharmaceutically acceptable vehicle; wherein said sustained release acrylic polymers are selected from the group consisting of: (1) a methacrylic acid type A copolymer, an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:1; (2) a methacrylic acid type B copolymer, an anionic copolymern based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:2; (3) a dimethylaminoethylacrylate/ethylmethacrylate copolymer, a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral (meth)acrylic acid esters is 1:20; and (4) an ethyl methacrylate/chlorotrimethylammoniumethyl methacrylate copolymer, a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral (meth)acrylic acid esters is 1:40. 2. A method of treating gingivitis, comprising topical application of efficacious amounts of a liquid polymer composition to the teeth or gingival tissues of an animal or human., said liquid polymer composition consisting essentially of: (a) one or more sustained release acrylic polymers; (b) a bacteriocidal pharmacological agent; (c) a release adjusting agent selected from the group consisting of a cross-linking agent, citric acid, a sodium citrate, sodium ducosate, and an amino acid; and (d) a pharmaceutically acceptable vehicle; wherein said sustained release acrylic polymers are selected from the group consisting of: (1) a methacrylic acid type A copolymer, an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:1; (2) a methacrylic acid type B copolymer, an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:2; (3) a dimethylaminoethylacrylate/ethylmethacrylate copolymer, a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral (meth)acrylic acid esters is 1:20; and (4) an ethyl methacrylate/chlorotrimethylammoniumethyl methacrylate copolymer, a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral (meth)acrylic acid esters is 1:40. 3. The method of claim 1, wherein said amino acid is selected from the group consisting of: lysine, aspartic acid, and glutaric acid. 4. The method of claim 1, wherein said bacteriocidal pharmacological agent is selected from the group consisting of an antibiotic and an antiseptic. 5. The method of claim 1, wherein said antibiotic is a bacteriocidal quaternary ammonium salt. 6. The method claim 5, wherein said bacteriocidal quaternary ammonium salt is selected from the group consisting of cetylpyridinium chloride and benzalkonium chloride. 7. The method of claim 6, wherein said bacteriocidal quaternary ammonium salt is cetylpyridinium chloride. 8. The method of claim 6, wherein said bacteriocidal quaternary ammonium salt is benzalkonium chloride. 9. The method of claim 2, wherein said amino acid is selected from the group consisting of: lysine, aspartic acid, and glutaric acid. 10. The method of claim 2, wherein said bacteriocidal pharmacological agent is selected from the group consisting of an antibiotic and an antiseptic. 11. The method of claim 10, wherein said antibiotic is a bacteriocidal quaternary ammonium salt. 12. The method claim 11, wherein said bacteriocidal quaternary ammonium salt is selected from the group consisting of cetylpyridinium chloride and benzalkonium chloride. 13. The method of claim 12, wherein said bacteriocidal quaternary ammonium salt is cetylpyridinium chloride. 14. The method of claim 12, wherein said bacteriocidal quaternary ammonium salt is benzalkonium chloride. |
| PATENT DESCRIPTION |
FIELD OF THE INVENTION The invention is directed to a liquid polymer composition which may be used in the treatment or prevention of dental or dermatological conditions such as fungal, bacterial, or viral infection, tooth hypersensitivity etc. The composition provides a sustained release of an active agent which may be an antiseptic, an antibiotic, a viricidal agent, or any other pharmacological agent. BACKGROUND OF THE INVENTION I. DENTAL CONDITIONS A. Prevention of Plaque Formation, Caries, and Periodontal Disease The relationship between bacterial plaque and the development of periodontal disease and caries has been thoroughly established (Axelsson, P., et al., J. Clin. Perio. 5:133-151 (1978)). Periodontal disease is a major problem in humans, especially in adults 40 years of age or older, in the mentally retarded, and in the handicapped. For the latter two groups in particular this is due to an inability to properly care for the teeth. Periodontal disease is also widespread among animals, especially housepets. It has also been clearly shown that the bacterial flora of the gingival crevice is important in the etiology of periodontal disease (Slots, J., J. Clin. Perio. 6:351-382 (1979)). Therefore, treatment of periodontal and caries diseases is directed to controlling this flora. The most widely used approach to date has been mechanical cleaning methods such as tooth brushing. Although this method has proved to be fairly successful in treating individuals, there is still a high recurrence rate. There is also the problem of motivating people to good oral hygiene habits that they will maintain throughout their lives. Although systemic administration of antibiotics has been shown to be a useful method of controlling the subgingival flora, discontinuation of therapy will result in the return of the potential pathogens to the pockets (Genco, R. J., J. Perio. 52:545-558 (1981)). Long-term antibiotic therapy has been used, but the potential dangers associated with this form of treatment, which include the development of resistant strains and superimposed infections, do not warrant its serious consideration. Antibacterial agents such as chlorhexidine and quaternary ammonium salts in the form of mouth rinses, dentifrices, solutions and gels have not proven to be successful in preventing periodontal disease (see, for example, Ciancio, S. G., et al., Pharm. Therap. Dent. 3:1-6 (1978)), as these agents are unable to affect the subgingival flora when administered in these forms (Goodson, J. M., et al., J. Clin. Perio. 6:83-92 (1979)). In addition, reported side effects of chlorhexidine, including staining and altered taste sensation, have resulted in limited usage. Attempts to reduce the staining and bitter taste by using dilute solutions and flavoring agents, respectively, have been only partially successful. Sustained release has been reported to be achieved by embedding chlorhexidine in an ethyl cellulose polymer to form a film (Friedman, M., et al., J. Perio. Res. 17:323-328 (1982); Friedman, M., et al., IADR Prog. and Abstr. 59:No. 905 (1980)). This dosage form was used in the local treatment of periodontal disease (Soskolne, W. A., et al., J. Perio. Res. 18:330-336 (1983)) and in the treatment of plaque prevention in patients wearing orthodontic appliances (Friedman, M., et al., J. Dent. Res. 64:1319-1321 (1985)). A drawback to this plaque preventative system was that although plaque accumulation was decreased by the application of a film composed of chlorhexidine embedded in an ethyl cellulose polymer, the effectiveness of the system in decreasing plaque accumulation was present only for a period of four days subsequent to administration of the film. Friedman, M., et al., (J. Dent. Res. 64:1319-1321 (1985)), concluded that "clearly the conditions in the oral cavity and the formulation used do not, at present, facilitate such prolonged prevention of plaque accumulation." These authors also suggested that by altering the film components and method of preparation it might be possible in clinical use to sustain the necessary level of antibacterial agent release for longer periods. No suggestion was made in this publication as to how this could be accomplished. Other antibacterial preparations for plaque prevention have been disclosed. Gaffar (U.S. Pat. No. 4,339,430) discloses an antibacterial oral composition containing an agent such as bis-biguanidohexanes or quaternary ammonium salts, and an additive which reduces staining of dental surfaces such as copolymers of glutamic acid, tyrosine, and alanine. This preparation was reported to be applied as a mouthwash or as a toothpaste. Wahmi (U.S. Pat. No. 4,374,824) discloses dentifrices for cleaning and preserving teeth. Disclosed were compositions comprising ginger, magnesium silicate, sodium chloride, catechu, alum, seed and shell of sweet almond, pyrethrum, gum mastic, and tobacco. It was reported that gum mastic was added to the composition to assist in the prevention of tooth decay. The disclosed compositions were intended to be in the form of toothpaste or tooth powders. This patent does not disclose the possible long-term anti-plaque effect of the compositions; further, application of the disclosed compositions two to three times per day is required for anti-plaque activity. Mastic has been used previously for other dental purposes. U.S. Pat. No. 4,668,188 (Wolfenson, G. B.) discloses the use of a curable mastic in the production of an oral impression tray for making impressions of teeth and jaw structures. Mastics have been used in the production of dental molds (U.S. Pat. No. 4,500,288, Von Weissenfluh, H.) and as an adhesive to secure dental articulators (U.S. Pat. Nos. 4,548,581 and 4,382,787, Hoffman, R. E.). U.S. Pat. Nos. 4,532,126 and 4,428,927 (Ebert, W. R., et al.) disclose chewable, filled, one-piece soft elastic gelatin capsules, made chewable by a masticatory substance, such as a synthetic mastic. U.S. Pat. No. 4,459,277 (Kosti, C. M.) relates to novel anti-plaque compositions for use in evaluating oral hygiene practices. In brief, the patent discloses a water-insoluble, water-immiscible dye emulsified in fine droplets or rupturable capsules. The patent discloses the use of mastic resin as well as alginates, and other gums as an insoluble media for dye dispersion. In particular, sodium carboxymethylcellulose is disclosed. Also disclosed is the possibility of incorporating antibacterial agents such as stannous fluoride into the compositions. Significantly, the Kosti patent is concerned with diagnostic rather than therapeutic applications. The patent fails to suggest compositions exhibiting long-term plaque preventive activity. U.S. Pat. No. 3,956,480 (Dichter et al.) discloses the use of an anionic polymer to sorb a cationic germicidal polymer to a tooth surface. A topical, sustained-release form of an antibacterial agent could help prevent the above-discussed side effects. Such a dosage form would be able to release the drug at a lower therapeutic level over a long period of time and thus might prevent the bitter taste and tooth staining. B. Treatment of Tooth Hypersensitivity Dental hypersensitivity, especially that arising from dentin and cementum hypersensitivity, is a frequently encountered problem in dentistry and a very troublesome clinical complaint. Hypersensitivity may occur wherever the dentin or cementum of a tooth is exposed by attrition or abrasion, or when the tooth's fine root surface is exposed by periodontal disease. In about 12% of erupted teeth, there is a developmental lack of protective covering of cementum at the cementoenamel junction. As a result, when the exposed dentin is subjected to mechanical, thermal, chemical or osmotic stimuli, the sensory nerves of the teeth become excited and a very painful response results. For example, people with hypersensitive teeth find it very painful to orally ingest certain forms of nourishment, such as liquids or foods that are hot or cold, sweet, hypertonic or contain citric acid. Everyday stimuli such as brushing the teeth may also be painful. Many attempts have been made to control hypersensitivity of the teeth. For example, U.S. Pat. No. 3,863,006 (Hodosh, M.) describes the use of potassium, lithium or sodium nitrate; U.S. Pat. Nos. 4,751,072 and 4,631,185 (both to Kim, S.) describe the use of potassium bicarbonate and potassium chloride; U.S. Pat. Nos. 4,710,372 and 4,634,589 (both to Scheller, H. U.) describe the use of hydroxyapatite or fluorapatite; U.S. Pat. No. 4,057,621 Pashley, D. H., et al.) describes the use of an alkali metal or ammonium oxalate; U.S. Pat. No. 4,415,549 (Shah, N. B.) describes the use of strontium EDTA, fluoride and ammonium glycyrrhizzinate; and, GB patent No. 990957 (Rosenthal, M. W.) describes the use of strontium for the control of hypersensitivity. The use of strontium ions to treat hypersensitivity was also disclosed in U.S. Pat. Nos. 3,122,483, 3,988,434 and 4,224,310. However, although clinically the most effective for reducing tooth hypersensitivity, the use of strontium salts for the treatment of hypersensitivity is disliked by patients due to the tendency of strontium salts to leave an unacceptably salty taste or metallic taste in the mouth, even when used in a toothpaste form. Another major disadvantage of strontium dentifrice is the long period of time of application which is required to achieve the clinical effect. A topical, sustained-release form of an agent capable of controlling dental hypersensitivity could help prevent undesirable taste side effects and still treat the hypersensitive condition. Such a dosage form would be able to release the agent controlling the hypersensitivity at a lower therapeutic level over a long period of time, for example, for weeks. Sustained localized release of the hypersensitivity agent, targeted directly to the hypersensitive site, would also solve the problem of the prolonged time and application currently required to obtain clinical effectiveness with strontium. C. Root Canal Sterilization A major concern in root canal dental procedures is the possibility of infection due to the introduction or cross-infection of bacteria, etc. into the affected region. Various surgical and endodontic methods have been developed in order to minimize the risk of infection (Miserendino, L. J., Oral Surg. Oral Med. Oral Pathol. 66:615-619 (1988); Mondragon, E. J., Pract. Odontol. 8:16-22 (1987); Herinsen, K. P. et al., Gen. Dent. 35:355-356 (1987); Levy, G. et al., Zahnarzt 30:441-442, 447-450 (1986); Chivian, N., Dent. Clin. North Amer. 28:637-649 (1984); Linke, H. A. et al., Oral Surg. Oral Med. Oral Pathol. 55:73-77 (1983); Agarwal, S. K. et al., J. Indian Dent. Assoc. 54:323-326 (1982), which references are incorporated herein by reference). Camphorated parachlorophenol (CPK) is an antibacterial agent used to treat bacterial contamination in the root canal. The usual treatment involves dipping an absorbent point or gauze into a CPK solution and placing it in the root canal. The absorbent point remains in the root canal until the next visit to the dentist. The primary disadvantage of the current treatment is the limited exposure time of the active material which may lead to re-infection of the root canal. II. FUNGAL INFECTIONS Microfungi can be classified as yeasts and filamentous fungi. Microfungi are capable of causing a variety of diseases in the oral cavity and the surrounding area. Mycotic diseases may arise as part of a systemic microfungal infection or may be derived from an independent infection which establishes in the oral cavity. Oral mycoses and their treatment are an important problem in oral medicine and have been reviewed in Kostiala, I. et al., Acta Odontol. Scand. 37:87-101 (1987), incorporated herein by reference. Many factors can predispose a patient to an opportunistic microfungal infection in the oral cavity. For example, general debilitation or poor oral hygiene are predisposing factors. Patients who are being treated with antibiotics, steroids, or cytostatic therapy, patients with AIDS, diabetes mellitus or other immunodeficiency or hormonal diseases, patients with malignant tumors or a hematogenous disorder are a high risk for opportunistic fungal infections. In addition, certain age groups such as infants, the elderly, and pregnant women are at a higher risk of oral fungal infections. Mechanical trauma from an ill-fitted prosthesis is also a major cause of oral microfungal infections. One report estimated that Candida was involved in 60% of the cases of "denture sore mouth" (denture stomatitis) in the elderly (Budtz-JZrgensen, E. et al., Community Dent. Oral Epidemiol. 3:115 (1975)). Denture stomatitis appears to be a manifestation of a cell-mediated hypersensitivity reaction to the microfungal infection. It is important to treat oral mycotic infections as soon as possible. Untreated infections may become the foci for systemic dissemination of the yeast or fungus, with potentially fatal result in severely compromised patients. For example, disseminated candidiasis is the second most common opportunistic infection in patients with AIDS (Odds, F. C., CRC Crit. Rev. Microbiol. 15:1-5 (1987)). The most important species of microfungi which have been implicated as being involved in superficial or deep mycotic infections in the oral cavity include Candida albicans, C. tropicalis, C. stellatoidea, C. pseudotropicalis, C. parapsilosis, C. guilliermondii, C. krusei, and C. vixwanathii, all of which have been implicated in candidiasis; Torulopsis glabrata which is the cause of torulpsidosis; Geotrichum candidum, which is the cause of geotrichosis; Rhizopus, Mucor, Absidia, and Basidiobolus which are the cause of aspergillosis, Cryptococcus neoformans, the cause of cryptococcosis; Blastomyces dermatitidis, the cause of blastomycosis; Paracoccidioides brasiliensis, the cause of paracoccidioidomycosis; Sporothrix schenkii, the cause of sporotrichosis; Rhinosporidium seeberi, the cause of rhinosporidoisis; Histoplasma capsulatum, the cause of histoplasmosis; Histoplasma duboisii, the cause of African histoplasmosis, Coccidiodes immities, the cause of coccidioidomycosis, Trichophyton mentagrophytes, T. rubrum, T. tonsurans, and T. violaceum, the causes of dennatophytosis; and, Rhinocladiella or Phialophora, and Cladosporium, the causes of chromomycosis. The Candida species is the most virulent of the fungi which infect the oral mucosa. Pathogenic Candida species are aerobic yeasts that can also grow anaerobically. C. albicans, the Candida species most often responsible for infections of the oral cavity, grows in two morphological forms: either as a budding yeast, or as a continuously extending hyphae which extends into tissue. In the oral cavity, Candida may cause a variety of disorders based on localization of the infection such as pulpitis, gingivitis, tonsillitis, cheilitis, glossitis, stomatitis, pharyngitis, laryngitis and sinusitis. Oral candidiasis has been classified into different categories based on the clinical and histopathological manifestations of the infection (Lehner, T., in Clinical Aspects of immunology, P. G. H. Gell, et al., eds., 3rd edition, Blackwell Scientific Publications, Oxford, 1975, pp. 1387-1427). Acute pseudomembranous candidiasis, or thrush, primarily affects children or patients with debilitating diseases (Crawson, R. A., Dent. Res. 15:361-364 (1965). C. albicans is a major causative agent of thrush in the newborn. The clinical signs which usually appear first are creamy-white, soft, nonkeratotic plaques which appear on the mucosa of the tongue, cheeks, gum and pharynx. The plaque is easily rubbed off, leaving an inflamed mucosa underneath. There may be no subjective symptoms until the plaque spreads to the pharynx, larynx or esophagus, where it may cause dysphaghia, soreness and dryness of the tongue, a sore throat or symptoms of cheilitis. Acute atrophic candidiasis is a form of thrush which is consistently painful, and which is thought to arise as a consequence of the shedding of the fungal plaque from its site of attachment to the tissue. It can be found on the dorsum linguae, or associated with angular cheilitis and inflammation of cheeks and lips. Chronic atrophic candidiasis, or denture stomatiffs is the term given to Candida-based infections of the denture-bearing tissues. Torulopsis glabrata is also associated with some forms of denture stomatiffs. Chronic mucocutaneous candidiasis refers to four different types of candidiasis which are resistant to treatment and which are associated with patients with a heterogeneous pattern of immunodeficiencies. These types of candidiasis include chronic oral hyperplastic candidiasis, which predominately affects adult males between the ages of 30 and 70; chronic localized mucocutaneous candidiasis, which starts in childhood as an intractable oral Candida infection and later manifests itself as lesions in the nails, and skin of the fingers and toes; chronic localized mucocutaneous candidiasis with granuloma which primarily affects young girls, starting in the mouth but later manifesting itself as horny masses of the face, scalp and upper respiratory tract; and, chronic localized mucocutaneous chadidosis with endocrine disorder, also found most frequently in young girls, and associated with lesions of the tongue, cheek, oral commissures and nails. The establishment of a mycotic infection in the oral cavity presents a serious health problem to the host which must be treated and contained. Treatment of mycotic diseases is directed to controlling this flora. The most widely used approach to date to control microfungi in the oral cavity has been mechanical cleaning methods such as brushing the teeth. Although this method has proved to be fairly successful in treating individuals, there is still a high recurrence rate. There is also the problem of motivating people to good oral hygiene habits that they will maintain throughout their lives. Systemic administration of antimycotics per os or intravenously has been used to control mycotic infections, however, discontinuation of therapy often results in the return of the pathogens to the oral cavity. Long-term systemic antimycotic therapy in doses high enough to control oral infections are undesirable for treatment of oral infections because the potential dangers and side-effects associated with this form of treatment include the development of resistant strains and superimposed infections, gastrointestinal irritation, liver damage and neurological symptoms, among others. Ridgway, F. et al., U.S. Pat. No. 4,725,440, describes a soft, antifungal drug-containing pastille or troche which is free of rough edges and will not adhere to oral mucosa, but which only releases anti-fungal medications within the 15-90 minutes while it dissolves in the mouth. Cyr et al., U.S. Pat. No. 3,312,594 describes long lasting troches or pastilles for the treatment of oral lesions which include an anhydrous adhesive based on pectin, gelatin and carboxymethylcellulose and which, when wetted, adhere to the oral mucous membranes. However, the Cyr formulation was not well-tolerated by patients (Ridgway, F. et al., U.S. Pat. No. 4,725,440). Antifungal agents have also been used in the form of mouth rinses, dentifrices, solutions and gels but have not proven to be completely successful in preventing fungal infections. A main problem with these techniques is that the antifungal drug does not remain in the oral cavity long enough at efficacious levels. Another serious problem with antifungal drugs is that they are by necessity directed towards controlling an infection by a eukaryotic fungal cell in a eukaryotic host. As a result, drugs effective against the fungus also tend to be toxic to the host. Thus is it important to develop methods which permit the localized, sustained application of the toxic drag in a manner and dosage which is efficacious but which minimizes toxicity the host. Especially, it is important to develop methods which use low doses of the drug. III. DERMATOLOGICAL CONDITIONS A dermatological disease or condition is one which affects the skin. Such conditions may reflect either the reaction of the immune system to a particular antigen or allergen, as is the case in rashes associated with allergic contact dermatitis (such as a reaction to poison ivy, poison oak, bee venom, etc.). Other dermatological conditions are caused by a variety of inflammatory causes (such as exfoliative dermatitis, eczematous dermatitis, pustules, psoriasis, urticaria, erythema multiforme syndrome, purpura, etc.). Yet other dermatological conditions may reflect bacterial infection (such as insect bites, impetigo, acne vulgaris, Lyme disease lesions, etc), fungal infection (such as ringworm, tinea versicolor, cutaneous candidiasis, molluscum contagiosum, etc.) or viral infection (such as warts, herpes simplex or zoster lesions, chicken pox lesions, rubella macules or papules, etc,). Yet another type of dermatological condition of concern to the present invention are burns, and especially sunburn. IV. SUMMARY The background art thus fails to identify any compositions of matter comprising a sustained-release carrier which can be used in conjunction with a bacteriocidal agent, for use as a sustained plaque preventative by humans and other animals, under conditions in which the agents have no deleterious medical side effects, and do not cause staining of the teeth. The background art also fails to identify any compositions of matter comprising an effective anti-hypersensitivity agent together with a long term sustained release carrier capable of providing efficacious levels of the anti-hypersensitivity agent, for use as a hypersensitivity preventative by humans and other animals, under conditions in which the anti-hypersensitivity agents have no undesirable side effects such as changes in taste sensations. A topical, sustained-release form of an antifungal agent, could help maintain a locally efficacious level of the antifungal drug in the oral cavity and prevent these side effects. Such a dosage form might also prevent undesirable systemic side effects by releasing the drug at a lower therapeutic level over a long period of time in a localized manner. A need therefore exists for a composition comprising a sustained-release carrier which could be used in conjunction with an anti-fungal, antibiotic, antiseptic, antiviral or other pharmacological agent, for use in the sustained release of such agent(s) in the prevention or therapy of dental, dermatological (and other) conditions of humans and other animals. It is particularly desirable that the antibacterial agent should be released from the composition, not only in a sustained fashion, but over a sufficiently long period of time so as not to require excessive application of the composition. SUMMARY OF THE INVENTION With the above-described needs in mind, the present inventors set out to find a composition which could be adapted to accomplish the sustained release of a pharmacological agent such as to permit its use in the treatment or prevention of dental or dermatological conditions. When attempting to use dental or dermatological agents in a liquid polymer composition consisting of methacrylic acid copolymer, two principal problems are encountered: (1) the hydrophilic nature of the copolymer causes rapid disintegration of the film, and in parallel, causes rapid release of the active agent; and (2) some agents may interact with the copolymer making it hydrophobic in nature, thus almost totally preventing release of the active agent from the film and slowing the disintegration process (i.e., non-degradable film). These problems have prevented the use of such a polymer as a matrix for the controlled release of drags to treat dental or dermatological conditions. The invention has, for the first time, solved these problems and, for the first time, allowed dental and dermatological agents to be provided to a subject in a controlled or sustained release manner in conjunction with acrylic polymers. Of particular concern to the present invention are oral conditions, including both conditions that are directly related to dental and periodontal disease (such as plaque, dental caries, periodontal disease, root canal infections, tooth extractions, tooth hypersensitivity, etc.) and conditions that are not directly related to dental and periodontal disease (such as oral candidiosis, pizza burns, tumors, aphthous ulcers, abscesses, denture stomatitis, halitosis, etc.), and including dental esthetics (tooth whitening, etc). The dermatological conditions of concern to the present invention include fungal infections, bacterial infections, viral infections, burns, insect bites, impetigo, tumors, etc. Of additional concern in the present invention is a composition and method of controlling the delivery of bone growth factors or alternatively of providing an occlusive membrane over a damaged bone and/or tissue, thereby enhancing the regenerative process. In detail, the invention provides a sustained-release liquid polymer composition which comprises: (a) a sustained release acrylic polymer; (b) a release adjusting agent (herein termed a "RAA"); and (c) a pharmacological agent; in a pharmaceutically acceptable vehicle, wherein the sustained release acrylic polymer is selected from the group consisting of EUDRAGIT L, EUDRAGIT S, EUDRAGIT RL, and EUDRAGIT RS. The invention further concerns the embodiment of the above-described composition wherein the pharmacological agent is selected from the group consisting of: an antibiotic, an antiseptic, an anti-fungal agent, an anti-viral agent, a bone and/or tissue growth factor, an anti-tumor agent, an anti-inflammatory agent and a hypersensitivity agent. The invention also concerns the embodiment of the above-described composition wherein the pharmacological agent is a bacteriocidal quaternary ammonium salt such as cetylpyridinium chloride or benzalkonium chloride or other bacteriocidal agent such as camphorated p-Chlorophenol (CPK). The invention also concerns the embodiment of the above-described composition wherein the pharmacological agent is a hypersensitivity agent (for example, a strontium salt such as strontium chloride or strontium citrate), a potassium salt (such as potassium chloride, potassium hydrogen tartrate, or potassium nitrate), a fluoride (such as stannous fluoride), or oxylates (such as potassium hydrogen oxylates). The invention also concerns the embodiment of the above-described composition wherein the pharmaceutically acceptable vehicle comprises an agent selected from the group consisting of water; ethyl alcohol; and ethyl alcohol and water. The invention also concerns the embodiment of the above-described composition which additionally contains a plasticizer, or polyethylene glycol or dibutyl phthalate. The invention also concerns the embodiment of the above-described composition where the release adjusting agent is selected from the group consisting of: a cross-linking agent, a polysaccharide, a lipid, a polyhydroxy compound, a protein such as Byco E or Byco C and an amino acid (for example, arginine or lysine), or a combination of the above release adjusting agents. The invention also provides a method of oral plaque prevention comprising topical application of the aforementioned liquid polymer composition to the teeth or gingival tissues of an animal or human. The invention also provides a method of treating oral infection comprising topical application of the aforementioned liquid polymer composition to the oral cavity of an animal or human. The invention also provides a method of treating tooth hypersensitivity comprising topical application of the aforementioned liquid polymer composition to the teeth or gingival tissues of an animal or human. The invention also provides a method of achieving root canal sterilization comprising topical application of the aforementioned liquid polymer composition to the teeth or gingival tissues of an animal or human. The invention also provides a method of treating a dermatological disease or condition comprising topical application of the aforementioned liquid polymer composition to the skin of an animal or human. The invention also provides a method of treating a dermatological disease or condition comprising topical application of the aforementioned liquid polymer composition to a mucosal tissue of an animal or human. The invention also provides an absorbent point, gauze, or film in combination with a controlled-release composition containing a liquid polymer and an active agent, especially CPK |
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